Differences In Risk Estimates Research Articles

Counseling and cryopreservation: evaluation of patient-reported counseling and choice on method of cancer-related fertility preservation.

Prior to cancer treatment, patients make decisions on whether to undergo fertility preservation (FP) and the method of FP. We sought to learn more about counseling and decision-making on the method of cancer-related FP. A cross-sectional 26-item online survey was administered to patients with ovaries who underwent cancer-related FP. Associations between demographics and the FP method were made through estimates of risk difference, with a 95% confidence interval. Open-ended responses were analyzed using the constant comparative method. A total of 240 respondents completed the survey: 52% underwent oocyte cryopreservation (OC), 29% underwent embryo cryopreservation (EC), and 19% underwent both oocyte and embryo cryopreservation (OC/EC). Most respondents agreed that if they were to go through the process again, they would make the same decision about FP (80% EC, 72% OC, 59% OC/EC). Women ≥ 35years reported being counseled more that embryos were superior compared to younger women (risk difference 46%, CI 32.8, 59.1), however were not more likely to freeze embryos (risk difference 6.2%, CI - 9.8, 22.2). Women in long-term relationships reported they were counseled more that embryos were superior compared to those single/dating (risk difference 27%, CI 18.1, 35.9). All women in long-term relationships reported undergoing EC, while the majority of single/dating women reported undergoing OC (74.6%). Most women who have undergone cancer-related FP reported they would choose the same FP method again. Women in long-term relationships or ≥ 35years reported they were more likely to be counseled that EC is superior; however, only women in long-term relationships were more likely to freeze embryos.

Variations in the use of oxytocin for augmentation of labour in Sweden: a population-based cohort study

National Swedish data shows substantial variation in the use of oxytocin for augmentation of spontaneous labour between obstetric units. This study aimed to investigate if variations in the use of oxytocin augmentation are associated with maternal and infant characteristics or clinical factors. We used a cohort design including women allocated to Robson group 1 (nulliparous women, gestational week ≥ 37 + 0, with singleton births in cephalic presentation and spontaneous onset of labour) and 3 (parous women, gestational week ≥ 37 + 0, with singleton births in cephalic presentation, spontaneous onset of labour, and no previous caesarean birth). Crude and adjusted logistic regression models with marginal standardisation were used to estimate risk ratios (RR) and risk differences (RD) with 95% confidence intervals (CI) for oxytocin use by obstetric unit. An interaction analysis was performed to investigate the potential modifying effect of epidural. The use of oxytocin varied between 47 and 73% in Robson group 1, and 10% and 33% in Robson group 3. Compared to the remainder of Sweden, the risk of oxytocin augmentation ranged from 13% lower (RD − 13.0, 95% CI − 15.5 to − 10.6) to 14% higher (RD 14.0, 95% CI 12.3–15.8) in Robson group 1, and from 6% lower (RD − 5.6, 95% CI − 6.8 to − 4.5) to 18% higher (RD 17.9, 95% CI 16.5–19.4) in Robson group 3. The most notable differences in risk estimates were observed among women in Robson group 3 with epidural. In conclusion, variations in oxytocin use remained despite adjusting for risk factors. This indicates unjustified differences in use of oxytocin in clinical practice.

The role of prescription opioid and cannabis supply policies on opioid overdose deaths.

Mandatory prescription drug monitoring programs and cannabis legalization have been hypothesized to reduce overdose deaths. We examined associations between prescription monitoring programs with access mandates ("must-query PDMPs"), legalization of medical and recreational cannabis supply, and opioid overdose deaths in United States counties in 2013-2020. Using data on overdose deaths from the National Vital Statistics System, we fit Bayesian spatiotemporal models to estimate risk differences and 95% credible intervals (CrI) in county-level opioid overdose deaths associated with enactment of these state policies. Must-query PDMPs were independently associated with on average 0.8 (95% CrI: 0.5, 1.0) additional opioid-involved overdose deaths per 100,000 person-years. Legal cannabis supply was not independently associated with opioid overdose deaths in this time period. Must-query PDMPs enacted in the presence of legal (medical or recreational) cannabis supply were associated with 0.7 (95% CrI: 0.4, 0.9) more opioid-involved deaths, relative to must-query PDMPs without any legal cannabis supply. In a time when overdoses are driven mostly by non-prescribed opioids, stricter opioid prescribing policies and more expansive cannabis legalization were not associated with reduced overdose death rates.

Evaluating recommendation-based dietary and physical activity strategies for prostate cancer prevention: a target trial emulation in the Health Professionals Follow-up Study.

The 2018 World Cancer Research Fund/American Institute for Cancer Research recommends sustained strategies of physical activity and diet for cancer prevention, but evidence for long-term prostate cancer risk is limited. Using observational data from 27,859 men in the Health Professionals Follow-up Study, we emulated a target trial of recommendation-based physical activity and dietary strategies and 26-year risks of prostate cancer, adjusting for risk factors via the parametric g-formula. Compared with no intervention, limiting sugar-sweetened beverages showed a 0.4% (0.0-0.9%) lower risk of lethal (metastatic or fatal) disease and 0.5% (0.1-0.9%) lower risk of fatal disease. Restricting consumption of processed foods showed a 0.4-0.9% higher risk of all prostate cancer outcomes. Estimated risk differences for clinically significant disease were close to null for strategies involving fruits and non-starchy vegetables, whole grains and legumes, red meat, and processed meat, as well as under a joint strategy of physical activity and diet. Compared with a "low adherence" strategy, maintaining recommended physical activity levels showed a 0.4% (0.1-0.8%) lower risk of lethal and 0.5% (0.2-0.8%) lower risk of fatal disease. Adhering to specific components of current physical activity and dietary recommendations may help to prevent lethal and fatal prostate cancer over 26 years.

Long-term ambient sulfur dioxide exposure during gestation and preterm birth in North Carolina, 2003–2015

BackgroundCoal-fired power plants are major contributors of ambient sulfur dioxide (SO2) air pollution. Epidemiological literature suggests an adverse association between SO2 exposure during gestation and preterm birth (PTB; <37 weeks completed gestation). PTB is strongly associated with infant mortality and increased risk for later life morbidities. ObjectiveWe investigated associations between SO2 and PTB in North Carolina and evaluated whether the associations were modified by race/ethnicity. MethodsWe assembled a retrospective, administrative cohort of singleton births in North Carolina from 2003 to 2015. We used US EPA EQUATES data to assign long-term SO2 gestational exposures to eligible births for the entire pregnancy and by trimester. We used multivariable generalized linear regression to estimate risk differences (RD (95%CI)) per 1-ppb increase in SO2, adjusted for gestational parent education, Medicaid status, marital status, and season of conception. Multi-pollutant models were additionally adjusted for other criteria air co-pollutants (O3, PM2.5, NO2). ResultsThe median SO2 (24-h average) across exposure windows was ∼1.5 (IQR: 1.8) ppb. The overall baseline risk for PTB was 8756 per 100,000 live births. When stratified by race/ethnicity, the baseline risk for PTB was 12215, 7824, and 7187 per 100,000 live births among non-Hispanic Black, non-Hispanic white, and Hispanic births, respectively. RDs per 1-ppb increase in SO2 averaged across the entire pregnancy were 317.0 (95%CI: 279.4, 354.5) and 568.2 (95%CI: 500.3, 636.1) per 100,000 live births for single- and multi-pollutant models, respectively. For the PTB multi-pollutant models, we observed similar RDs for non-Hispanic Black participants (669.6 [95%CI: 573.9, 765.2]) and non-Hispanic white participants (635.4 [95%CI: 557.2, 713.6]) with smaller RDs for Hispanic participants (336.8 [95%CI: 241.3, 432.2]). SignificanceThe results for our adjusted single- and multi-pollutant models showed adverse associations between SO2 and PTB, with some evidence of effect measure modification by race/ethnicity within subcategories of PTB.

Early vs Late Anticoagulation in Minor, Moderate, and Major Ischemic Stroke With Atrial Fibrillation

Whether infarct size modifies the treatment effect of early vs late direct oral anticoagulant (DOAC) initiation in people with ischemic stroke and atrial fibrillation is unknown. To assess whether infarct size modifies the safety and efficacy of early vs late DOAC initiation. Post hoc analysis of participants from the multinational (>100 sites in 15 countries) randomized clinical Early Versus Later Anticoagulation for Stroke With Atrial Fibrillation (ELAN) trial who had (1) acute ischemic stroke, (2) atrial fibrillation, and (3) brain imaging available before randomization. The ELAN trial was conducted between October 2017 and December 2022. Data were analyzed from October to December 2023 for this post hoc analysis. Early vs late DOAC initiation after ischemic stroke. Early DOAC initiation was within 48 hours for minor or moderate stroke or on days 6 to 7 for major stroke; late DOAC initiation was on days 3 to 4 for minor stroke, days 6 to 7 for moderate stroke, and days 12 to 14 for major stroke. The primary outcome was a composite of recurrent ischemic stroke, symptomatic intracranial hemorrhage, extracranial bleeding, systemic embolism, or vascular death within 30 days. The outcome was assessed according to infarct size (minor, moderate, or major) using odds ratios and risk differences between treatment arms. Interrater reliability for infarct size between the core laboratory and local raters was assessed, and whether this modified the estimated treatment effects was also examined. A total of 1962 of the original 2013 participants (909 [46.3%] female; median [IQR] age, 77 [70-84] years) were included. The primary outcome occurred in 10 of 371 participants (2.7%) with early DOAC initiation vs 11 of 364 (3.0%) with late DOAC initiation among those with minor stroke (odds ratio [OR], 0.89; 95% CI, 0.38-2.10); in 11 of 388 (2.8%) with early DOAC initiation vs 14 of 392 (3.6%) with late DOAC initiation among those with moderate stroke (OR, 0.80; 95% CI, 0.35-1.74); and in 8 of 219 (3.7%) with early DOAC initiation vs 16 of 228 (7.0%) with late DOAC initiation among those with major stroke (OR, 0.52; 95% CI, 0.21-1.18). The 95% CI for the estimated risk difference of the primary outcome in early anticoagulation was -2.78% to 2.12% for minor stroke, -3.23% to 1.76% for moderate stroke, and -7.49% to 0.81% for major stroke. There was no significant treatment interaction for the primary outcome. For infarct size, interrater reliability was moderate (κ = 0.675; 95% CI, 0.647-0.702) for local vs core laboratory raters and strong (κ = 0.875; 95% CI, 0.855-0.894) between core laboratory raters. The treatment effect of early DOAC initiation did not differ in people with minor, moderate, or major stroke assessed by brain imaging. Early treatment was not associated with a higher rate of adverse events, especially symptomatic intracranial hemorrhage, for any infarct size, including major stroke. ClinicalTrials.gov Identifier: NCT03148457.

The performance of marginal structural models for estimating risk differences and relative risks using weighted univariate generalized linear models.

We used Monte Carlo simulations to compare the performance of marginal structural models (MSMs) based on weighted univariate generalized linear models (GLMs) to estimate risk differences and relative risks for binary outcomes in observational studies. We considered four different sets of weights based on the propensity score: inverse probability of treatment weights with the average treatment effect as the target estimand, weights for estimating the average treatment effect in the treated, matching weights and overlap weights. We considered sample sizes ranging from 500 to 10,000 and allowed the prevalence of treatment to range from 0.1 to 0.9. We examined both the robust variance estimator when using generalized estimating equations with an independent working correlation matrix and a bootstrap variance estimator for estimating the standard error of the risk difference and the log-relative risk. The performance of these methods was compared with that of direct weighting. Both the direct weighting approach and MSMs based on weighted univariate GLMs resulted in the identical estimates of risk differences and relative risks. When sample sizes were small to moderate, the use of an MSM with a bootstrap variance estimator tended to result in the most accurate estimates of standard errors. When sample sizes were large, the direct weighting approach and an MSM with a bootstrap variance estimator tended to produce estimates of standard error with similar accuracy. When using a MSM to estimate risk differences and relative risks, in general it is preferable to use a bootstrap variance estimator than the robust variance estimator. We illustrate the application of the different methods for estimating risks differences and relative risks using an observational study on the effect on mortality of discharge prescribing of a beta-blocker in patients hospitalized with acute myocardial infarction.

Association Between Tranexamic Acid and Decreased Periprosthetic Joint Infection Risk in Patients Undergoing Total Hip and Knee Arthroplasty: A Systematic Review and Meta-Analysis of Over 2 Million Patients

BackgroundThe purpose of this study was to perform a systematic review and meta-analysis to evaluate the association between tranexamic acid (TXA) use during primary total hip arthroplasty (THA) and primary total knee arthroplasty (TKA), and the risk of developing periprosthetic joint infection (PJI) after these procedures. MethodsA systematic review was carried out from inception to October 17, 2022. There were 6 studies that were ultimately included in the meta-analysis. The association between the development of PJI and TXA was analyzed using odds ratios (ORs) with 95% confidence intervals (CIs) and estimates of risk difference (RD). Subgroup analysis was performed to evaluate only studies reporting out to 90 days of follow-up versus more than 90 days of follow-up. ResultsAmong 2,098,469 arthroplasties, TXA utilization was associated with an overall lower risk of PJI (OR = 0.63 [95% CI 0.42 to 0.96], P < .001) and a 0.4% lower incidence of PJI (RD = −0.0038, 95% CI [-0.005 to −0.002], P < .001). When subgrouping the studies according to length of follow-up, TXA was associated with a lower risk of PJI (OR = 0.43 [95% CI 0.35 to 0.53], P < .001) and a 1% lower incidence of PJI (RD = −0.0095 [95% CI −0.013 to −0.005], P < .001) in patients followed for more than 90 days. ConclusionsThis meta-analysis demonstrates that TXA use is associated with a reduced risk of PJI, with our RD analysis identifying an approximately 0.4% reduction in PJI rates with TXA use. These findings provide even more data to support the routine use of TXA during primary THA and primary TKA.

Bayesian approach to assessing population differences in genetic risk of disease with application to prostate cancer.

Population differences in risk of disease are common, but the potential genetic basis for these differences is not well understood. A standard approach is to compare genetic risk across populations by testing for mean differences in polygenic scores, but existing studies that use this approach do not account for statistical noise in effect estimates (i.e., the GWAS betas) that arise due to the finite sample size of GWAS training data. Here, we show using Bayesian polygenic score methods that the level of uncertainty in estimates of genetic risk differences across populations is highly dependent on the GWAS training sample size, the polygenicity (number of causal variants), and genetic distance (FST) between the populations considered. We derive a Wald test for formally assessing the difference in genetic risk across populations, which we show to have calibrated type 1 error rates under a simplified assumption that all SNPs are independent, which we achieve in practise using linkage disequilibrium (LD) pruning. We further provide closed-form expressions for assessing the uncertainty in estimates of relative genetic risk across populations under the special case of an infinitesimal genetic architecture. We suggest that for many complex traits and diseases, particularly those with more polygenic architectures, current GWAS sample sizes are insufficient to detect moderate differences in genetic risk across populations, though more substantial differences in relative genetic risk (relative risk > 1.5) can be detected. We show that conventional approaches that do not account for sampling error from the training sample, such as using a simple t-test, have very high type 1 error rates. When applying our approach to prostate cancer, we demonstrate a higher genetic risk in African Ancestry men, with lower risk in men of European followed by East Asian ancestry.

Clinical Outcomes of Rapid Respiratory Virus Testing in Emergency Departments

Rapid tests for respiratory viruses, including multiplex panels, are increasingly available in emergency departments (EDs). Their association with patient outcomes remains unclear. To determine if ED rapid respiratory virus testing in patients with suspected acute respiratory infection (ARI) was associated with decreased antibiotic use, ancillary tests, ED length of stay, and ED return visits and hospitalization and increased influenza antiviral treatment. Ovid MEDLINE, Embase (Ovid), Scopus, and Web of Science from 1985 to November 14, 2022. Randomized clinical trials of patients of any age with ARI in an ED. The primary intervention was rapid viral testing. Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting guidelines were followed. Two independent reviewers (T.S. and K.W.) extracted data and assessed risk of bias using the Cochrane Risk of Bias, version 2.0. Estimates were pooled using random-effects models. Quality of evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluations framework. Antibiotic use and secondary outcomes were pooled separately as risk ratios (RRs) and risk difference estimates with 95% CIs. Of 7157 studies identified, 11 (0.2%; n = 6068 patients) were included in pooled analyses. Routine rapid viral testing was not associated with antibiotic use (RR, 0.99; 95% CI, 0.93-1.05; high certainty) but was associated with higher use of influenza antivirals (RR, 1.33; 95% CI, 1.02-1.75; moderate certainty) and lower use of chest radiography (RR, 0.88; 95% CI, 0.79-0.98; moderate certainty) and blood tests (RR, 0.81; 95% CI, 0.69-0.97; moderate certainty). There was no association with urine testing (RR, 0.95; 95% CI, 0.77-1.17; low certainty), ED length of stay (0 hours; 95% CI, -0.17 to 0.16; moderate certainty), return visits (RR, 0.93; 95%, CI 0.79-1.08; moderate certainty) or hospitalization (RR, 1.01; 95% CI, 0.95-1.08; high certainty). Adults represented 963 participants (16%). There was no association of viral testing with antibiotic use in any prespecified subgroup by age, test method, publication date, number of viral targets, risk of bias, or industry funding. The results of this systematic review and meta-analysis suggest that there are limited benefits of routine viral testing in EDs for patients with ARI. Further studies in adults, especially those with high-risk conditions, are warranted.

Impact of Alcohol Consumption on Breast Cancer Incidence and Mortality: The Women's Health Study.

Background: Alcohol intake is associated with breast cancer (BC) risk, but estimates of greatest public health relevance have not been quantified in large studies with long duration. Materials and Methods: In this prospective cohort study of 39,811 women (median 25 years follow-up), we examined the association between alcohol consumption and BC incidence and mortality with adjusted hazard ratios (HRs), cubic splines, absolute risks, number needed to harm (NNH), and population-attributable fractions. Results: We documented 2,830 cases of BC, including 237 BC deaths. Each additional alcoholic drink/day was associated with a 10% higher rate (HR = 1.10, 95% confidence intervals [CIs]: 1.04-1.16) of total BC in a linear manner (p = 0.0004). The higher rate was apparent for estrogen receptor (ER)+ (HR = 1.12, 95% CI: 1.06-1.18) but not ER- tumors (HR = 0.95, 95% CI: 0.82-1.10), with a statistically significant difference between these associations (p = 0.03). We constructed models comparing BC incidence among 100,000 women followed for 10 years. Compared to a scenario where all women rarely or never consumed alcohol, we expect 63.79 (95% CI: 58.35-69.24) more cases (NNH = 1,567) had all women consumed alcohol at least monthly and 278.66 (95% CI: 268.70-288.62) more cases (NNH = 358) had all women consumed >1 drink/day. Approximately 4.1% of BC cases were attributable to consumption exceeding one drink/month. Conclusion: Alcohol consumption is associated with a linear dose-response increase in BC incidence even within recommended limits of up to one alcoholic drink/day, at least for ER+ tumors. Our estimates of risk differences, attributable fraction, and NNH quantify the burden that alcohol consumption imposes on women in the general population. ClinicalTrials.gov Identifier: NCT00000479.

Risk of venous thromboembolism in patients with rheumatoid arthritis: a meta-analysis of observational studies

BackgroundThrombotic events, such as venous thromboembolism (VTE) are a major health complication linked to rheumatoid arthritis (RA). We performed a meta-analysis to evaluate the risk of VTE, including deep vein thrombosis (DVT) and pulmonary embolism (PE), in adults with RA compared to the general population.MethodsMEDLINE and EMBASE databases were searched from inception to April 2022 to identify publications meeting the following criteria: (1) prospective and retrospective original data from cohort or case-control studies; (2) pre-specified RA definition; (3) clearly defined VTE outcomes; (4) reported risk estimate and 95% confidence intervals (95% CIs); (5) at least sex- and age-matched to comparison group; and (6) English language. Of 372 studies screened, 14 were included (602,760 RA patients, 123,076 VTE events) and their quality was assessed by an adaptation of the STROBE quality scoring scale.ResultsThe pooled risk ratios of VTE, DVT and PE in patients with RA were 1.57 (95% CI 1.41–1.76), 1.58 (95% CI 1.26–1.97) and 1.57 (95% CI 1.30–1.88), respectively. The I2 value of 92%, 94% and 92% for VTE, DVT and PE analyses, suggesting considerable heterogeneity. There were no significant differences in risk estimates among the five subgroup analyses: quality score (P = 0.35, I2 = 0%); sex (P = 0.31, I2 = 1.7%); study year (P = 0.81, I2 = 0%); population source (P = 0.35, I2 = 0%); study design (P = 0.62, I2 = 0%).ConclusionsResults show that patients with RA are at a higher risk of VTE, DVT and PE compared to the general population.

Comparison of the Efficacies of Topical Liposomal Amphotericin B and Topical Clotrimazole in the Treatment of Pityriasis Versicolor.

Pityriasis versicolor (PV) often exhibits recurrence even despite treatment, and a standardized therapy with a complete cure rate remains elusive. Given the fungicidal property of amphotericin B, its potential for PV treatment warrants investigation. This study aimed to compare the efficacy of topical liposomal amphotericin B and clotrimazole cream in treating PV. A randomized controlled trial was conducted with 44 PV patients, aged 15 to 70 years, who were equally assigned to either the amphotericin or clotrimazole group. The trial was registered at the Iranian Registry of Clinical Trials on March 7th, 2022. PV diagnosis was confirmed in all patients through positive microscopic results. The amphotericin group received topical gel containing liposomal amphotericin B 0.4%, while the other group received topical cream containing clotrimazole 1%. Both treatments were applied twice daily to the affected skin lesions for 14 days. The primary outcomes assessed were mycologic cure, clinical cure, and complete cure at day 14 post-treatment. Both drugs demonstrated successful treatment outcomes, with comparable rates of mycologic cure (77.3%), clinical cure (63.6%), and complete combined cure (63.6%). There was no significant difference between the groups in terms of the degree of cure (P=0.75). Adjustments for age, sex, lesion extent, and lesion site yielded insignificant risk ratio and risk difference estimates for the complete cure rate (P>0.05).

Preoperative Exclusive Enteral Nutrition Is Associated With Reduced Skin and Soft Tissue and Intra-abdominal Infections in Patients With Crohn's Disease Undergoing Intestinal Surgery: Results from a Meta-Analysis.

Malnutrition is an independent risk factor for adverse postoperative outcomes and is common among patients with Crohn's disease (CD). The objective of this meta-analysis was to precisely quantify the association of preoperative exclusive enteral nutrition (EEN) and total parenteral nutrition (TPN) with surgical outcomes in patients undergoing intestinal surgery for CD. PubMed, Embase, and Scopus were queried for comparative studies evaluating the impact of preoperative nutritional support on postoperative outcomes in patients undergoing surgery for CD. Random effects modeling was used to compute pooled estimates of risk difference. Heterogeneity was assessed using I2. Fourteen studies, all nonrandomized cohort studies, met inclusion criteria for studying EEN. After pooling data from 14 studies (874 EEN treated and 1044 control patients), the relative risk of intra-abdominal septic complications was decreased 2.1-fold in patients receiving preoperative EEN (relative risk 0.47, 95% confidence interval [CI], 0.35-0.63, I2 = 0.0%). After pooling data from 9 studies (638 EEN treated and 819 control patients), the risk of skin and soft tissue infection was decreased 1.6-fold (relative risk 0.63; 95% CI, 0.42-0.94, I2 = 42.7%). No significant differences were identified in duration of surgery, length of bowel resected, or operative blood loss. Among the 9 studies investigating TPN, no significant differences were identified in infectious outcomes. Preoperative nutritional optimization with EEN was associated with reduced risk of infectious complications in CD patients undergoing intestinal surgery. Preoperative nutritional support with EEN should be considered for optimizing outcomes in CD patients requiring bowel resection surgery.

Interval estimation of common risk difference for stratified unilateral and bilateral data✩

ABSTRACT In clinical trials, unilateral or bilateral data can usually be encountered if a subject contributes one or both of paired organs. For the bilateral data, responses from two paired body parts are correlated. In this paper, we study various confidence intervals of common risk difference in stratified unilateral and bilateral data based on the Dallal’s model. Simulation results show that the score method outperforms other methods and provides coverage probability close to the nominal level and satisfactory coverage width. Hence, the method is recommended. In addition, the inverse hyperbolic tangent Wald-type become as optimal as the score method with the increase of sample sizes. An otolaryngology example is used to demonstrate the proposed methods.

How Far Can Interventions to Increase Income Improve Adolescent Mental Health? Evidence From the UK Millennium Cohort Study and Next Steps

UK adolescents and young adults are facing increasing rates of mental health problems and extremely difficult economic circumstances. There is strong evidence that interventions to increase income during adolescence can mitigate conditions such as anxiety and depression. However, policymakers lack quantified risk differences in the probability of mental illness between different income groups by which to establish the prospective scale of mitigation. Here, we estimate risk differences using two longitudinal cohort studies: Millennium Cohort Study (cohort members born between 2000 and 2002) and Next Steps (born 1989–1990). We quantify the association between income and risk of depression at age 14, serious mental illness at age 17, and non-psychotic mental illness at age 25. We also conduct sensitivity analysis using numerous other markers of socioeconomic (SES) status. We estimate that those living in the poorest quintile group of households have a greater probability of mental health problems than the richest at ages 14, 17, and 25. We find that other markers of SES status—subjective financial strain, cohort member assessed wealth relative to friends, occupational class, and education—display steeper associations with mental health symptoms relative to associations between mental health symptoms and income. Our findings are likely to be conservative underestimates since they are likely to be attenuated by well-known and large measurement errors in both mental health problems and living standards during adolescence.

PP41 Using Medicare Claims Data To Support Reimbursement Of A Novel Leadless Pacing System For The Management Of Bradycardia

IntroductionThe Micra Transcatheter Pacing System (Micra TPS) is a single-chamber transcatheter leadless pacemaker (LPM). LPMs do not require leads or a subcutaneous pocket, which represent the primary sources of device-related complications with conventional transvenous pacemakers (TVPMs). Complications such as infections and lead dislodgements cause significant patient burden, which have significant economic consequences. Running a randomized controlled trial (RCT) to estimate risk differences of infrequent events requires large sample sizes and long follow-up periods. Real-world observational data, while informative, requires an appropriate study design and statistical adjustments to control for potential biases.MethodsThe Micra Coverage with Evidence Development (CED) study was a cohort study of LPM versus TVPM based on US Medicare claims data of 16,431 patients with 2-year follow up (LPM: n=6,219; TVPM: n=10,212). Propensity score matching (PSM) was applied to account for differences in baseline characteristics. As no RCT was identified in the literature, this study was presented to the Australian payer as the primary source of clinical evidence, upon which a cost-utility analysis was conducted.ResultsAfter PSM, the CED study demonstrated significantly more complications with TVPM versus LPM with adjusted rates of 6.5 percent and 4.6 percent (p&lt;0.001). Significant differences favoring LPM (p&lt;0.01) were observed in device breakdown (1.4% vs 2.0%), dislodgment (0.4% vs 1.2%) and infection (&lt;0.1% vs 0.6%). Based on these findings, a claim of superior safety was accepted by Medical Services Advisory Committee (MSAC) to support reimbursement. In making this decision, MSAC considered that the large sample size and propensity weighting overcame some of the potential biases and the magnitude of the benefit supported cost-effectiveness relative to TVPM.ConclusionsThe lack of a sufficiently powered RCT with an extended follow-up period can mean the impact and benefits of new technologies that reduce clinically important adverse events of relative infrequency are not formally incorporated into payer decision making, particularly where RCTs are a requirement. A well-designed observational study can provide valuable, real-world evidence to support a HTA for reimbursement decisions.

Racial disparities in treatment initiation between Black and White older adults with multiple myeloma: A SEER-Medicare analysis.

145 Background: We have previously identified racial disparities in multiple myeloma (MM) treatment initiation within 12 months of diagnosis. Black MM patients (60.6%) were significantly less likely to initiate treatment than White MM patients (69.5%). This current study aimed to explore the extent to which Black/White (B/W) disparities in MM treatment initiation were explained by differences in the distribution of demographic and health characteristics. Methods: We identified Black and White adults (66+) diagnosed with MM 2007 to 2017 in linked SEER-Medicare data. Patients were required to have 12 months of continuous Medicare Parts A and B pre- and post-diagnosis and Medicare Part D for 12 months post-diagnosis or until death. Our outcome was MM treatment initiation within 12 months of diagnosis and our independent variable was race (Black or White) as identified in SEER. Covariates thought to confound the relationship between race and MM treatment initiation were added to successive binomial regression models to estimate risk differences and 95% confidence limits (CL). Model 1 included only race. Model 2 added age and sex. Model 3 added Medicare low-income subsidy status and census tract poverty. Model 4 added rurality and SEER region. Model 5 added comorbidity and predicted frailty. Results: Our cohort (n=10,666) consisted of 1,649 Black and 9,017 White older adults with MM. Distributions of all individual, area-level and health characteristics differed significantly by race. In bivariate analysis all characteristics, except for sex and rurality, were significantly associated with treatment initiation. B/W risk differences remained significant across models and ranged from 3.7% (CL=0.9, 6.5) to 10.7% (CL=8.2, 13.2). Covariates explained some, but not all, of the B/W disparities in MM treatment initiation (Table 1). Conclusions: After accounting for differences in demographic and health characteristics, Black MM patients remained significantly less likely to initiate treatment within 12 months. Our study identified several factors that if addressed could attenuate B/W treatment initiation disparities. Further investigation is needed to understand how these factors contribute to treatment disparities, in order to develop health equity interventions to address them. Our results also suggest that there are additional unidentified factors contributing to disparity in MM treatment initiation. These factors must be identified and explored as we work to eliminate B/W disparities in MM treatment.[Table: see text]

Trends in Maternal Weight Disparities: Statewide Differences in Rural and Urban Minnesota Residents From 2012 to 2019.

Despite research showing substantial weight disparities along the rural-urban continuum, little work has attempted to identify differences in prepregnancy weight status or gestational weight gain (GWG) outcomes between rural and urban birthing people. As such, the goals of this research were to 1) document the prevalence of prepregnancy overweight and obesity and excessive GWG in rural and urban birthing people and 2) examine changes in rural and urban prepregnancy overweight or obesity and excessive GWG over time. Birth certificate data provided sociodemographic variables, prepregnancy body mass index, GWG, and rurality status on 465,709 respondents who gave birth in Minnesota from 2012 to 2019. A series of regression models estimated risk differences in 1) prepregnancy weight status and 2) excessive GWG between rural and urban respondents over time, controlling for relevant covariates. Rural individuals had a 4.9 percentage-point (95% confidence interval, 4.5-5.3) higher risk of having prepregnancy overweight or obesity compared with urban individuals, and a 2.6 percentage-point (95% confidence interval, 1.9-3.3) higher risk of gaining excessive gestational weight. The disparities in prepregnancy overweight or obesity and excessive gestational weight between rural and urban individuals widened over time. These findings contribute to accumulating evidence documenting notable health disparities between rural and urban individuals during the perinatal period and support the need to develop prevention and treatment efforts focused on improving the weight-related health of individuals living in rural communities.

Risk ratio and risk difference estimation in case-cohort studies.

In case-cohort studies with binary outcomes, ordinary logistic regression analyses have been widely used because of their computational simplicity. However, the resultant odds-ratio estimates cannot be interpreted as relative risk measures unless the event rate is low. The risk ratio and risk difference are more favorable outcome measures that are directly interpreted as effect measures without the rare disease assumption. We provide pseudo-Poisson and pseudo-normal linear regression methods for estimating the risk ratio and risk difference in analyses of case-cohort studies. These multivariate regression models are fitted by weighting the inverses of sampling probabilities. Also, the precisions of the risk ratio and risk difference estimators can be improved using auxiliary variable information, specifically by adapting the calibrated or estimated weights, which are readily measured on all samples from the whole cohort. Finally, we provide computational code in R (R Foundation for Statistical Computing, Vienna, Austria) that can easily perform these methods. Through numerical analyses of artificially simulated data and the National Wilms Tumor Study data, accurate risk ratio and risk difference estimates were obtained by the pseudo-Poisson and pseudo-normal linear regression methods. Also, using the auxiliary variable information from the whole cohort, precisions of these estimators were markedly improved. The ordinary logistic regression analyses may provide uninterpretable effect measure estimates, and the risk ratio and risk difference estimation methods are effective alternative approaches for case-cohort studies. These methods are especially recommended under situations in which the event rate is not low.